Accurate prognosis and prediction of overall and cancer specific survival at the time of prostate cancer diagnosis are of utmost importance for the improvement of current status of personalized treatment choice between radical prostatectomy, radiation therapy, castration therapy and watchful waiting (Shariat et al, Cancer 2008, 113:3075-3099; Touijer et al, Cancer 2009, 115:3107-3111; Freedland, Cancer 2011, 117:1123-1153). Radical prostatectomy and curative radiation therapy for men with localized prostate cancer can reduce mortality and prolong lives for patients with aggressive cancer. On the other hand for patients with less aggressive cancer, that potentially need no radical or curative treatments at all, such therapies may cause unnecessary complications and side effects. For patients with less aggressive cancer watchful-waiting or active surveillance can be a suitable option. However, current prognostic and predictive methods based on common clinical parameters—including age at diagnosis, serum PSA level, Gleason score of biopsies and clinical stage—cannot accurately distinguish between less aggressive and aggressive cancers at localized stage. Nor can they identify what kind of cancer can still be effectively controlled by castration therapy when the disease becomes dangerous.
For patients whose cancers are already advanced at diagnosis or have relapsed after curative treatments chemical or surgical castration can palliate symptoms and slow down disease progression. Unfortunately, the effect and side effects of castration therapy show strong variation among patients. Some can live longer than five years with minimal side effects whereas others can die of castration resistant metastasis within three years or die of cardiovascular and other side effects of the castration treatment. Currently there are no methods that can predict what kind of patients would be benefit most from castration therapy.
A majority of prostate cancers progress so slowly that they can never reach the life-threatening stage, mainly due to old age and other competing diseases. However, a small proportion of prostate cancers progress very rapidly and kill patients in less than five years. At diagnosis, by conventional clinical parameters including age, tumor grade, Gleason score, clinical stage and comorbidity the prediction of cancer specific and overall survival can reach an accuracy up to 60-70%. Even patients with the same clinical prognostic parameters can show strong difference in survival as well as in response to treatment. Hence prostate cancer is a pathological (morphorlogical) diagnosis that may include several different biological subgroups or subtypes.
There is a need for a method that can distinguish these biological subgroups or subtypes of prostate cancer patients. There is also a need for a method that can classify these subtypes into aggressive or high risk tumors and less aggressive or low risk tumors, as well as a method that can predict survival of the patients with the respective subtype tumor. Furthermore, there is a need for a method that can be used for making a treatment decision for patients that have a tumor of the respective subtype, possibly also taking into account clinical parameters.